The objective of this proposal is to determine the modes of metabolic activation of the major environmental polynuclear aromatic hydrocarbon carcinogaens, 2-methylfluoranthene, 3-methylfluoranthene, benzo(b)fluoranthene, benzo(j)fluoranthene, benzo(k)fluoranthene, dibenzo(a,h)pyrene, dibenzo(a,i)pyrene, dibenzo)a,1)pyrene, indeno(1,2,3-c,d)-pyrene, dibenzo(c,g)carbazole, and dibenz(a,j)acridine. These polycylic hydrocarbons were specifically selected for study on the basis of human exposure. The methods proposed for the isolation and structural elucidation of proximate carconigens employ a combination of high pressure liquid chromatography and mutagenicity assays in S. typhimurium. Structural elucidation of isolated proximate carcinogens will be confirmed by unequivocal synthesis. The tumorigenic potential of suspect proximate carcinogens will be determined on mouse skin. We have already employed this approach in studies on the activation of benzofluoranthenes, fluoranthenes, dibenzo(a,h)pyrene, and dibenzo(a,i)pyrene. Metabolic activation pathways indicated by these studies will be further evaluated by synthesis of the suspect ultimate carcinogens, bioassays in newborn mice, and identification of the major DNA-adducts of the parent hydrocarbon formed in vivo. The influence of environmental modifiers on metabolic activation in vitro and DNA binding in vivo will then be determined. These studies will lead to an understanding of the mechanism of action of these select polynuclear aromatic hydrocarbons which are of particular importance because of their widespread environmental occurrence.